Tumors are dependent upon new blood vessel formation, or angiogenesis, for expansive growth. Our prior analysis of gene expression in tumor endothelium led to the identification of a G-protein coupled receptor called TEM5. In an attempt to understand the role of TEM5 in angiogenesis and its importance for tumor growth, we previously embarked upon a hunt for its physiological ligand. Through a number of serendipitous events we have now come across what appears to be another soluble molecule capable of evoking angiogenesis. We are currently characterizing this factor and its role in tumorigenesis.